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Morphogenetic Variability as Potential Biomarker of Functional Outcome After Ischemic Stroke.

ABSTRACT: The aim of our study was to evaluate the role of morphogenetic variability in functional outcome of patients with ischemic stroke. The prospective study included 140 patients with acute ischemic stroke, all of whom were tested upon: admission; discharge; one month post-discharge; and three months post-discharge. The age was analyzed, as well. The Functional Independence Measure (FIM) test and the Barthel Index (BI) were used for the evaluation of functional outcomes for the eligible participants. We analyzed the presence of 19 homozygous recessive characteristics (HRC) in the studied individuals. There was a significant change in FIM values at discharge (p = 0.033) and in BI values upon admission (p = 0.012) with regards to the presence of different HRCs. Age significantly negatively correlated for the FIM score and BI values at discharge for the group with 5 HRCs (p < 0.05), while for BI only, negative significant correlation was noticed for the group with 5 HRCs at three months post-discharge (p < 0.05), and for the group with 3 HRCs at one month post-discharge (p < 0.05) and three months post-discharge (p < 0.05). Morphogenetic variability might be one among potentially numerous factors that could have an impact on the response to defined treatment protocols for neurologically-impaired individuals who suffered an ischemic stroke.

SUBMITTER: Savic M

PROVIDER: S-EPMC6627147 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Morphogenetic Variability as Potential Biomarker of Functional Outcome After Ischemic Stroke.

Savic Milan M Cvjeticanin Suzana S Lazovic Milica M Nikcevic Ljubica L Petronic Ivana I Cirovic Dragana D Nikolic Dejan D

Brain sciences 20190614 6

The aim of our study was to evaluate the role of morphogenetic variability in functional outcome of patients with ischemic stroke. The prospective study included 140 patients with acute ischemic stroke, all of whom were tested upon: admission; discharge; one month post-discharge; and three months post-discharge. The age was analyzed, as well. The Functional Independence Measure (FIM) test and the Barthel Index (BI) were used for the evaluation of functional outcomes for the eligible participants ...[more]

PMID: 31197109

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Project description:Background and Purpose- We sought to explore the effect of genetic imbalance on functional outcome after ischemic stroke (IS). Methods- Copy number variation was identified in high-density single-nucleotide polymorphism microarray data of IS patients from the CADISP (Cervical Artery Dissection and Ischemic Stroke Patients) and SiGN (Stroke Genetics Network)/GISCOME (Genetics of Ischaemic Stroke Functional Outcome) networks. Genetic imbalance, defined as total number of protein-coding genes affected by copy number variations in an individual, was compared between patients with favorable (modified Rankin Scale score of 0-2) and unfavorable (modified Rankin Scale score of ?3) outcome after 3 months. Subgroup analyses were confined to patients with imbalance affecting ohnologs-a class of dose-sensitive genes, or to those with imbalance not affecting ohnologs. The association of imbalance with outcome was analyzed by logistic regression analysis, adjusted for age, sex, stroke subtype, stroke severity, and ancestry. Results- The study sample comprised 816 CADISP patients (age 44.2±10.3 years) and 2498 SiGN/GISCOME patients (age 67.7±14.2 years). Outcome was unfavorable in 122 CADISP and 889 SiGN/GISCOME patients. Multivariate logistic regression analysis revealed that increased genetic imbalance was associated with less favorable outcome in both samples (CADISP: P=0.0007; odds ratio=0.89; 95% CI, 0.82-0.95 and SiGN/GISCOME: P=0.0036; odds ratio=0.94; 95% CI, 0.91-0.98). The association was independent of age, sex, stroke severity on admission, stroke subtype, and ancestry. On subgroup analysis, imbalance affecting ohnologs was associated with outcome (CADISP: odds ratio=0.88; 95% CI, 0.80-0.95 and SiGN/GISCOME: odds ratio=0.93; 95% CI, 0.89-0.98) whereas imbalance without ohnologs lacked such an association. Conclusions- Increased genetic imbalance was associated with poorer functional outcome after IS in both study populations. Subgroup analysis revealed that this association was driven by presence of ohnologs in the respective copy number variations, suggesting a causal role of the deleterious effects of genetic imbalance.

Project description:BackgroundMixed data exist regarding the association between hyperglycemia and functional outcome after acute ischemic stroke when accounting for the impact of leptomeningeal collateral flow. We sought to determine whether collateral status modifies the association between treatment group and functional outcome in a subset of patients with large vessel occlusion enrolled in the Stroke Hyperglycemia Insulin Network Effort (SHINE) trial.MethodsIn this post-hoc analysis, we analyzed patients enrolled into the SHINE trial with anterior circulation large vessel occlusion who underwent imaging with CT angiography prior to glucose control treatment group assignment. The primary analysis assessed the degree to which collateral status modified the effect between treatment group and functional outcome as defined by the 90-day modified Rankin Scale score. Logistic regression was used to model the data, with adjustments made for thrombectomy status, age, post-perfusion thrombolysis in cerebral infarction (TICI) score, tissue plasminogen activator (tPA) use, and baseline National Institutes of Health Stroke Scale (NIHSS) score. Five SHINE trial centers contributed data for this analysis. Statistical significance was defined as a p-value < 0.05.ResultsAmong the 1151 patients in the SHINE trial, 57 with angiographic data were included in this sub-analysis, of whom 19 had poor collaterals and 38 had good collaterals. While collateral status had no effect (p = 0.855) on the association between glucose control treatment group and functional outcome, patients with good collaterals were more likely to have a favorable functional outcome (p = 0.001, OR 5.02; 95% CI 1.37-16.0).ConclusionsIn a post-hoc analysis using a subset of patients with angiographic data enrolled in the SHINE trial, collateral status did not modify the association between glucose control treatment group and functional outcome. However, consistent with prior studies, there was a significant association between good collateral status and favorable outcome in patients with large vessel occlusion stroke.Trial registrationClinicalTrials.gov Identifier is NCT01369069. Registration date is June 8, 2011.

Project description:Currently, few studies are reported on the composition of microbiota in stroke patients and the association with stroke prognosis. This study investigated the differing microbiota composition in stroke patients and confirmed the association of microbiota composition with poor functional outcome. Between January of 2018 and December of 2019, 198 patients with acute cerebral infarction were included in this study. For the case-control study, age and sex-matched normal healthy subjects (n = 200) were included when receiving their health screening examinations. We isolated bacterial extracellular membrane vesicles and extracted DNA from blood samples. Taxonomic assignments were performed by using the sequence reads of 16S rRNA genes following blood microbiota analysis. Statistical analysis was conducted appropriately by using Statistical Analysis System software. The mean age of the stroke patients were 63.7 ± 12.5 years, and the male sex was 58.5%. Of the total enrolled patients, poor functional outcome (modified Rankin Score ≥ 3) was noted in 19.7%. The principal component analysis of microbiota composition revealed significant differences between healthy control subjects and stroke patients. At the genus level, Aerococcaceae(f), ZB2(c), TM7-1(c), and Flavobacterium were significantly increased in stroke patients compared to the healthy controls, whereas Mucispirillum, rc4-4, Akkermansia, Clostridiales(o), Lactobacillus, and Stenotrophomonas were decreased considerably. For the functional outcome after ischemic stroke, Anaerococcus, Blautia, Dialister, Aerococcaceae(f), Propionibacterium, Microbacteriaceae(f), and Rothia were enriched in the group with good outcomes, whereas Ruminococcaceae(f) and Prevotella were enriched in the group with poor outcome. There was apparent dysbiosis of blood microbiota in patients with acute ischemic stroke compared to healthy people. Ruminococcaceae(f) and Prevotella were elevated in stroke patients with poor functional outcome.

Project description:IntroductionStroke remains a leading cause of death and disability worldwide. Effective and prompt prognostic evaluation is vital for determining the appropriate management strategy. Radiomics is an emerging noninvasive method used to identify the quantitative imaging indicators for predicting important clinical outcomes. This study was conducted to investigate and validate a radiomics nomogram for predicting ischemic stroke prognosis using the modified Rankin scale (mRS).MethodsA total of 598 consecutive patients with subacute infarction confirmed by diffusion-weighted imaging (DWI), from January 2018 to December 2019, were retrospectively assessed. They were assigned to the good (mRS ≤ 2) and poor (mRS > 2) functional outcome groups, respectively. Then, 399 patients examined by MR scanner 1 and 199 patients scanned by MR scanner 2 were assigned to the training and validation cohorts, respectively. Infarction lesions underwent manual segmentation on DWI, extracting 402 radiomic features. A radiomics nomogram encompassing patient characteristics and the radiomics signature was built using a multivariate logistic regression model. The performance of the nomogram was evaluated in the training and validation cohorts. Ultimately, decision curve analysis was implemented to assess the clinical value of the nomogram. The performance of infarction lesion volume was also evaluated using univariate analysis.ResultsStroke lesion volume showed moderate performance, with an area under the curve (AUC) of 0.678. The radiomics signature, including 11 radiomics features, exhibited good prediction performance. The radiomics nomogram, encompassing clinical characteristics (age, hemorrhage, and 24 h National Institutes of Health Stroke Scale score) and the radiomics signature, presented good discriminatory potential in the training cohort [AUC = 0.80; 95% confidence interval (CI) 0.75-0.86], which was validated in the validation cohort (AUC = 0.73; 95% CI 0.63-0.82). In addition, it demonstrated good calibration in the training (p = 0.55) and validation (p = 0.21) cohorts. Decision curve analysis confirmed the clinical value of this nomogram.ConclusionThis novel noninvasive clinical-radiomics nomogram shows good performance in predicting ischemic stroke prognosis.

Dataset Information

Morphogenetic Variability as Potential Biomarker of Functional Outcome After Ischemic Stroke.

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Morphogenetic Variability as Potential Biomarker of Functional Outcome After Ischemic Stroke.

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